Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present investigation was carried out to evaluate the antioxidant nature of ethanolic extract of Terminalia arjuna bark (EETA) on N-nitrosodiethylamine (DEN) induced liver cancer in male Wistar albino rats. Liver cancer was induced by single intraperitonial injection of DEN (200 mg/kg). After 2 weeks of DEN administration, Phenobarbital (PB) was given to promote the cancer for up to 14 successive weeks. EETA extract (400 mg/kg) was given post-orally for 28 days to hepatocellular carcinoma-bearing rats. After the experimental period, all the animals were sacrificed and serum, liver and kidney samples were collected for further biochemical analysis. The levels of lipid peroxides (LPO) under basal and also in the presence of inducers (H(2)O(2), ascorbate and FeSO(4)) were estimated in serum, liver and kidney of control and experimental animals. Enzymic antioxidants, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-enzymic antioxidants like Vitamin C (Vit-C) and Vitamin E (Vit-E) levels were determined in all the groups of animals. A significant increase in LPO levels were observed while the levels of enzymic and non-enzymic antioxidants were decreased, when subjected to DEN induction. These altered enzyme levels were ameliorated significantly by administration of EETA at the concentration of 400 mg/kg in drug-treated animals. This protective effect of EETA was associated with inhibition of LPO induced by DEN and to maintain the antioxidant enzyme levels. Our results show an antioxidant activity of T. arjuna bark against DEN-induced liver cancer.
Mol Cell Biochem 2006 Jan
PMID:Antioxidant activity of Terminalia arjuna bark extract on N-nitrosodiethylamine induced hepatocellular carcinoma in rats. 1632 60

Among numerous gene therapeutic strategies for cancer treatment, gene transfer by conditionally replicative adenovirus (CRAd) of interferon-gamma (IFN-gamma) may be useful because of the possibility that it will yield IFN-gamma-mediated antiangiogenesis, immune responses, and CRAd-mediated oncolysis. In this study, we constructed a human TERT promoter-mediated oncolytic adenovirus targeting telomerase-positive cancers and armed with a mouse or human IFN-gamma gene to generate novel immune gene-viral therapeutic systems, CNHK300-mIFN-gamma and CNHK300-hIFN-gamma, respectively. The systems can specifically target, replicate in, and lyse cancer cells, while sparing normal cells. The advantage of these systems is that the number of transgene copies and their expression increase markedly via viral replication within infected cancer cells, and replicated viral progeny can then infect additional cancer cells within the tumor mass. CNHK300-mIFN-gamma induced regression of xenografts in liver cancer models in both immunodeficient and immunocompetent mice by triplex mechanisms including selective oncolysis, antiangiogenesis, and immune responses. We conclude that combining immune gene therapy and oncolytic virotherapy can enhance antitumor efficacy as a result of synergism between CRAd oncolysis and transgene composite antitumor responses.
Mol Ther 2006 May
PMID:Immune gene-viral therapy with triplex efficacy mediated by oncolytic adenovirus carrying an interferon-gamma gene yields efficient antitumor activity in immunodeficient and immunocompetent mice. 1649 59

This paper presents a comparison of the dipole moment derivatives with respect to internal coordinates in the liquid and gas phases for benzene-h(6), benzene-d(6) and benzene-d(1). The literature values of the integrated intensities of the infrared active fundamentals of the three gaseous isotopomers are used to determine the dipole moment derivatives with respect to internal coordinates, using the methods described in the previous paper for the liquid phase. As was found for the liquid phase in the previous paper, there is uncertainty surrounding the intensities of the individual CH stretching fundamentals of benzene-d(1) due to intensity sharing with active combinations. The magnitudes of the dipole moment derivatives with respect to internal coordinates in the gas phase are partial differentialmicro/ partial differentials=0.50+/-0.03DA(-1), partial differentialmicro/ partial differentialt=0.28+/-0.03, partial differentialmicro/ partial differentialbeta=0.24+/-0.01, and partial differentialmicro/ partial differentialgamma=0.65+/-0.02DA(-1), where s, t, beta and gamma are the CH stretching, and CC stretching, the HCC bending and the HCCC torsion displacements, respectively. The experimental intensities are different for the three isotopomers in the liquid and gas phases, and the calculations show that these differences are mainly due to a difference between the CH stretch dipole moment derivatives in the two phases. This difference was related qualitatively to the intermolecular interaction of the H with the pi-cloud of the nearest neighbour creating a pseudo-hydrogen bond.
Spectrochim Acta A Mol Biomol Spectrosc 2006 Nov
PMID:Dipole moment derivatives with respect to the internal coordinates of benzene in the liquid and gas phases. 1651 Mar 6

The protective potentials of a potentized homeopathic drug, Lycopodium-30, prepared from extract of spores of a plant, Lyocopodium clavatum (Fam: Lycopodiaceae) and used as a remedy for various liver ailments, have been tested in mice chronically fed p-dimethyl amino azo benzene (p-DAB) - an initiator, and phenobarbital (PB) - a promoter of hepatic cancer, by using some cytogenetic endpoints like chromosome aberrations (CA), micronuclei (MN), mitotic index (MI) and sperm head abnormality (SHA), and toxicity biomarkers like acid and alkaline phosphatases (AcP and AlkP, respectively), alanine and aspartate amino transferases (ALT and AST, respectively) and lipid peroxidation (LPO) and reduced glutathione (GSH) activities. The effects of chronic treatment of the carcinogens were assessed at different intervals of fixation, namely, at day 7, 15, 30, 60, 90 and day 120, and compared with that of mice fed conjointly with the carcinogens and the homeopathic remedy. Both the assay systems indicated considerable protective potentials of the homeopathic remedy against p-DAB induced hepatocarcinogenesis in mice.
Mol Cell Biochem 2006 Apr
PMID:Protective potentials of a potentized homeopathic drug, Lycopodium-30, in ameliorating azo dye induced hepatocarcinogenesis in mice. 1653 99

Hepatocellular carcinoma (HCC), the major manifestation of primary liver cancer, is one of the most frequent and malignant cancers worldwide, especially in Taiwan. Estrogen receptors (ERs) have been reported to play either a proliferation- or apoptosis-enhancing role in the differentiation of cancers, including HCC. In a previous experiment, we showed that transient overexpressed estrogen receptor-alpha induced early stage HCC cell line Hep 3B cell apoptosis by increasing the hTNF-alpha gene expression in a ligand-independent manner. To further clarify if the apoptotic effect occurs in poorly differentiated HCC cell line, HA22T, and elucidate the roles of ERs and TNF-alpha, DNA fragmentation and caspase activity were measured in late stage HCC cell line, HA22T, by measuring the expression of hER-alpha and hER-beta using a Tetracycline-inducible system (Tet-on). Increased DNA fragmentation and caspase-3 activity were found in hERbeta-overexpressed HA22T cells treated with estrogen (10(-8) M) but not in hERalpha-overexpressed HA22T cells. Using RT-PCR/PCR and western blotting in HA22T cells, overexpressed hER-beta was also found to increase the expression of hTNF-alpha mRNA and induce hTNF-alpha-dependent luciferase activity in a ligand-dependent manner. Additionally, LPS treatment and hER-beta overexpression both enhance caspase-8 activities, whereas neither hER-beta nor E2 treatment affected caspase-9 activities. In addition, the overexpressed hER-beta plus E2 enhanced DNA fragmentation and caspase-8 activities were only partially reduced by anti-hTNF-alpha (0.1 ng/ml), which was possibly due to the involvement of P53 and TGF-beta. Taken together, our data indicates that overexpressed hER-beta but not hER-alpha may induce caspase-8-mediated apoptosis by increasing the hTNF-alpha gene expression in a ligand-dependent manner in poorly differentiated HA22T cells.
Mol Cell Biochem 2006 Jul
PMID:Opposing action of estrogen receptors alpha and beta on tumor necrosis factor-alpha gene expression and caspase-8-mediated apoptotic effects in HA22T cells. 1663 37

AREG (Amphiregulin), BTC (beta-cellulin), EGF, EPGN (Epigen), EREG (Epiregulin), HBEGF, NRG1, NRG2, NRG3, NRG4 and TGFA (TGFalpha) constitute EGF family ligands for ERBB family receptors. Cetuximab (Erbitux), Pertuzumab (Omnitarg) and Trastuzumab (Herceptin) are anti-cancer drugs targeted to EGF family ligands, while Gefitinib (Iressa), Erlotinib (Tarceva) and Lapatinib (GW572016) are anti-cancer drugs targeted to ERBB family receptors. AREG and TGFA are biomarkers for Gefitinib non-responders. The TCF/LEF binding sites within the promoter region of human EGF family members were searched for by using bioinformatics and human intelligence (Humint). Because three TCF/LEF-binding sites were identified within the 5'-promoter region of human AREG gene, comparative genomics analyses on AREG orthologs were further performed. The EPGN-EREG-AREG-BTC cluster at human chromosome 4q13.3 was linked to the PPBP-CXCL segmental duplicons. AREG was the paralog of HBEGF at human chromosome 5q31.2. Chimpanzee AREG gene, consisting of six exons, was located within NW_105918.1 genome sequence. Chimpanzee AREG was a type I transmembrane protein showing 98.0% and 71.4% total amino-acid identity with human AREG and mouse Areg, respectively. Three TCF/LEF-binding sites within human AREG promoter were conserved in chimpanzee AREG promoter, but not in rodent Areg promoters. Primate AREG promoters were significantly divergent from rodent Areg promoters. AREG mRNA was expressed in a variety of human tumors, such as colorectal cancer, liver cancer, gastric cancer, breast cancer, prostate cancer, esophageal cancer and myeloma. Because human AREG was characterized as potent target gene of WNT/beta-catenin signaling pathway, WNT signaling activation could lead to Gefitinib resistance through AREG upregulation. AREG is a target of systems medicine in the field of oncology.
Int J Mol Med 2006 Jun
PMID:Canonical WNT signaling pathway and human AREG. 1668 31

Although ribosomal proteins are major components of ribosomes, recent data have shown them to have extraribosomal functions apart from ribosome and protein biosynthesis. In our earlier study, we showed that ribosomal protein L13 mRNA was up-regulated in response to DNA damage in hamster cells. We report here that L13 expression is up-regulated in human gastrointestinal cancers. We also examined the biological role of L13 on human cancer cells. Knocking down L13 expression using small interfering RNA (siRNA) resulted in drastic attenuation of cancer cell growth with significant G1 and G2/M arrest of the cell cycle. Moreover, L13 siRNA significantly enhanced the cellular sensitivity to certain DNA damaging agents and, concordantly, L13-overexpressing cells demonstrated greater chemoresistance compared to parent cells, suggesting an inverse correlation between L13 expression and chemosensitivity. By using semiquantitative RT-PCR, we analyzed expression of L13 in freshly resected cancer tissue of the stomach, colorectum and liver. Up-regulation of L13 mRNA expression was observed in 10 (28%) of 36 gastric, 19 (41%) of 46 colorectal and 5 (20%) of 25 liver cancer tissue samples compared to adjacent normal tissue samples. We also found that increased expression of the L13 gene correlated with clinical staging in gastric cancers. The results of this study suggest that L13 plays an essential role in the progression of some gastrointestinal malignancies.
Int J Mol Med 2006 Jul
PMID:Activation of the ribosomal protein L13 gene in human gastrointestinal cancer. 1678 68

We previously identified a novel cancer/testis antigen gene CAGE by screening cDNA expression libraries of human testis and gastric cancer cell lines with sera of gastric cancer patients. CAGE is expressed in many cancers and cancer cell lines, but not in normal tissues apart from the testis. In the present study, we investigated its role in the motility of cells of two human cancer cell lines: HeLa and the human hepatic cancer cell line, SNU387. Induction of CAGE by tetracycline or transient transfection enhanced the migration and invasiveness of HeLa cells, but not the adhesiveness of either cell line. Overexpression of CAGE led to activation of ERK and p38 MAPK but not Akt, and inhibition of ERK by PD98059 or p38 MAPK by SB203580 counteracted the CAGE-promoted increase in motility in both cell lines. Overexpression of CAGE also resulted in a reduction of ROS and an increase of ROS scavenging, associated with induction of catalase activity. Inhibition of ERK and p38 MAPK increased ROS levels in cells transfected with CAGE, suggesting that ROS reduce the motility of both cell lines. Inhibition of ERK and p38 MAPK reduced the induction of catalase activity resulting from overexpression of CAGE, and inhibition of catalase reduced CAGE-promoted motility. We conclude that CAGE enhances the motility of cancer cells by activating ERK and p38 MAPK, inducing catalase activity, and reducing ROS levels.
Mol Cells 2006 Jun 30
PMID:CAGE, a novel cancer/testis antigen gene, promotes cell motility by activation ERK and p38 MAPK and downregulating ROS. 1681 99

The investigation of differentially expressed proteins was used together with other techniques to study the inhibitory effects of two different doses of berberine in human liver cancer cell line HepG2. For HepG2 cells treated with 24.0 mg l(-1) of berberine, an increase in the sub G(0) phase that was indicative of cell death was observed in cell cycle analysis with flow cytometry. However, no significant increase in sub G(0) was observed in HepG2 cells treated with 4.0 mg l(-1) of berberine. Using flow cytometric analysis, significant activation of caspase 3 was not observed with HepG2 cells treated with 4.0 and 24.0 mg l(-1) of berberine. In this work, labeling of cells with stable isotope was not used in the proposed method developed. The whole cell lysates from the control and treated cells were digested with trypsin and the peptides were separated by two-dimensional (cation exchange and reversed phase) liquid chromatography and tandem mass spectrometry. Our preliminary data showed that the proposed platform provided a rapid approach to study the molecular mechanism due to the inhibitory effects of different doses of the berberine on HepG2 cell lines. This included a network of proteins involved in mitogen-activated protein kinase (MAPK) phosphorelay systems, metabolism, regulation of cell cycle and DNA damage response. The differentially expressed proteins identified using the current approach were consistent with the data obtained from cell cycle analysis with flow cytometry.
Mol Biosyst 2006 May
PMID:Investigation of differentially expressed proteins due to the inhibitory effects of berberine in human liver cancer cell line HepG2. 1688 Sep 43

Targeted oncolytic viruses and immunostimulatory therapeutics are being developed as novel cancer treatment platforms. These approaches can be combined through the expression of immunostimulatory cytokines from targeted viruses, including adenoviruses and herpesviruses. Although intratumoral injection of such viruses has been associated with tumor growth inhibition, eradication of distant metastases was not reported. The major limitations for this approach to date have been (1) inefficient intravenous virus delivery to tumors and (2) the lack of predictive, immunocompetent preclinical models. To overcome these hurdles, we developed JX-594, a targeted, thymidine kinase(-) vaccinia virus expressing human GM-CSF (hGM-CSF), for intravenous (i.v.) delivery. We evaluated two immunocompetent liver tumor models: a rabbit model with reproducible, time-dependent metastases to the lungs and a carcinogen-induced rat liver cancer model. Intravenous JX-594 was well tolerated and had highly significant efficacy, including complete responses, against intrahepatic primary tumors in both models. In addition, whereas lung metastases developed in all control rabbits, none of the i.v. JX-594-treated rabbits developed detectable metastases. Tumor-specific virus replication and gene expression, systemically detectable levels of hGM-CSF, and tumor-infiltrating CTLs were also demonstrated. JX-594 holds promise as an i.v.-delivered, targeted virotherapeutic. These two tumor models hold promise for the optimization of this approach.
Mol Ther 2006 Sep
PMID:Systemic armed oncolytic and immunologic therapy for cancer with JX-594, a targeted poxvirus expressing GM-CSF. 1684 20


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